DE2657370C2 - Means for covering and / or filling in bone defects - Google Patents

Description

50

The invention relates to a means for covering and / or filling in bone defects, in particular for inserting endosseous implants.

In the case of bone defects, as in the case of small bones, occur during operations and implantations in bone tissue, a considerable amount arises in each case Risk of infection, this is particularly great with endosseous half-implants, i.e. h, in those cases where μ the bone tissue and a foreign body implanted in it are no longer completely removed from the tissue are closed and part of the foreign body looks beyond the surface of the soft tissue, because in this case during the healing process between the tissue and the implantal body Bacteria can enter. Instead of the ImDlantal growing into the Ktiöchenköroer, it comes then often to an inflammation of the surrounding tissue, which leads to the rejection of the implant or at least for intussusception of soft tissue between implant and bone. This will be the chances of success of such interventions are significant decreased. Especially when inserting dental half-implants, As they are used recently on a larger scale, this results in considerable Difficulty wedging. You're trying to get there the gap between to keep the bone tissue and the implant as small as possible in order to ensure that the To ensure implant, so that this is soon resilient. This gap is too small for a To allow escape of any inflammable substances, on the other hand, however, so large that he a Ingress of bacteria from the oral cavity is allowed. Similar problems also exist with the cementless insertion of hip joints, as has recently been the case with practiced in younger patients.

The present invention is therefore based on the object of a means for covering and / or filling of bone defects, especially for the insertion of intra-osseous implants, to create the one sterile Closure of the wound surfaces allows and spaces between bone tissue and implants allowed to be filled in and that dissolved or resorbed during the regrowth or ingrowth of the bone will. This object is achieved according to the invention by a solution of physiological saline solution and at least one gellable polysaccharide and / or gelatin, the solution being liquid in one Temperature which is above body temperature, but below a temperature at which the body tissue Is permanently damaged or coagulated, and when cooled to body temperature a stable gel forms. The term physiological saline solution is used here in a broader sense, and should also be such Solutions include, in which a physiological saline solution in the narrower sense known blood substitute substances are mixed in.

The agent according to the invention is applied to the wound surfaces at a temperature above the The solidification temperature of the solution to form the gel is, however, below the temperature at which a permanent Damage or coagulation of the tissue occurs, which is the case between 50 ° and 53 ° C. When inserting of intra-osseous dental implants, the wall of the bone cavity with the Middle 'covers or the whole bone cavity is filled with it. Then the implant is inserted, so that the entire area between the wall of the bone cavity and the implant of the agent is filled out. Since this immediately solidifies to a gel when it cools down to body temperature, it becomes from the wound exudate is not flushed out immediately, so that it enters the wound cavity during the beginning of the Healing process completes sterile. However, the choice of materials ensures that the agent is dissolved or resorbed with increasing ingrowth of the bone tissue and not as an intermediate layer between the implant to be held and the Bone tissue remains.

Although it is known from DE-OS 21 54 272, the Pores of a porous outer layer of an implant with a dried layer before use from a water soluble substance, e.g. B. gelatin or the like, to seal and to sterilize or antibacterial treatment of this substance, whereby

this layer is dissolved after implantation by the body fluids, so that the tissue cells in the can now grow in free pores.

According to a particularly preferred embodiment, the agent according to the invention contains a substance that promotes tissue diffusion, in particular hyaluronidase, in an amount of 7 IU to 800 IU, preferably 60 IU to 90 IU per cm ^{1 of} the liquefied agent. The substance that promotes tissue diffusion, which is enclosed in the gel, diffuses into the adjacent tissue, there supports the breakdown of Blulger islets and the blood circulation necessary for reorganization, as well as the removal of waste products.

The agent furthermore preferably contains 0.05 mg to 500 mg of an anti-bacterial and / or sulfonamide per cm ^{3 of} the liquefied agent. As a result of the inclusion in the gel, a depot effect of the antibotic and / or sulfonamide is achieved, which in normal cases is immediately flushed out of the wound cavity due to the formation of the wound secretion. In connection with the tissue-promoting substance, that is, its introduction into the surrounding tissue is facilitated, the depth effect of the antibotic or sulfonamide is also improved.

It is particularly useful if the agent contains an addition of substances that promote bone growth that can slowly diffuse from the gel to any forming bone without being prematurely washed out to become. For implant ingrowth, apatite crystals are preferably used in the gel powdered Jingebrachl, which is known strongly accelerate bone regeneration. Such Apatile crystals can be made from calcium-aluminum-phosphate, for example exist. Their resorption creates ions at the interfaces that cause the Promote the build-up of new bone tissue. This advantage could not be used with the previous techniques as the apatites were quickly flushed out and their dosage to the points of interest was difficult.

Sodium, lithium, magnesium, Borate, fluoride, phosphate, calcium, potassium ions, carbon and / or silicon compounds that are used in physical form are added to the agent, with sodium, calcium, boron and phosphate ions in particular are beneficial. The ability of the above ions to promote growth of bone tissue on dense aluminum oxide ceramic is known from DE-AS 23 24 867. These ions are there diffused into the surface of the implants by thermal diffusion, including a expensive and large technical effort is necessary. Another difficulty with this procedure is that Dosage of ions and the length of time for which they are released into the tissue. In the inventive Medium lets the dosage Ηργ ions through control the admixture to the solution more easily.

Particularly in those cases in which large cavities are to be filled with the new bone to be formed, it is advisable to use a variant of the agent according to the invention in which a denatured bone meal is added to the liquefied agent. This portion of the bone meal is expediently 2.5 wt>% to 60 wt .-%, preferably 5Gcw ° / o to 20 wt. ₁ - ¹ Vo, based on the amount of the liquefied agent.

Agar products or agar derivatives are preferably used as polysaccharides which are part of the agent according to the invention. At these körpervenräglichen substances it is particularly favorable that their freezing point is about 40 ⁰ C. as

ΐ Agarose, which is found in Depending on the concentration, solidifies to form a gel between approximately 35 ° C and 41 "C.

The agent according to the invention for covering and / or filling in bone defects contains as

ίο gel-forming solution according to a particularly advantageous one Embodiment a 0.6 wt .-% to 30 wt .-%, preferably a 2 wt .-% to 2.5 wt .-% Solution of agarose in physiological saline solution.

Egg, expedient method for producing the agent for covering and / or filling in bone defects, especially for the insertion of intra-osseous implants, consists in that one in physiological Saline solution has at least one polysaccharide

2Q and / or gelatin for dissolution and sterilization cooks, the type and amount of the at least one polysaccharide and / or the gelatin being measured that a stable gel is formed when cooling to body temperature, and that the resulting solution is kept at a temperature above the solidification temperature of the gel until it is used, especially at about 5 (5 'C.

The resulting solution can be about 2.5 wt .-% to about 60 wt .-%, preferably about 5 wt .-% to about 20% by weight of denatured bone meal, based on the amount of liquefied agent, and / or bone-forming or bone growth-promoting substances, preferably apatite crystals in Powder form, and / or sodium, lithium, magnesium, borate, fluoride, phosphate, calcium, potassium ions, Carbon and / or silicon compounds are added in body-soluble form.

In a modification of the method described above, at least one ·} polysaccharide and / or the gelatin before it is dissolved and boiled in the physiological saline solution, for example 2.5% by weight to about 60% by weight, preferably about 5% by weight to about 20% by weight of a denatured Bone meal, based on the amount of liquefied agent, and / or substances that promote bone wax, preferably apatite crystals in powder form, and / or sodium, lithium, magnesium, borate, Fluoride, phosphate, calcium, potassium ions, carbon and / or silicon compounds in body-soluble

^w rather form admitted. A dry substance is thus chosen that contains at least one gel-forming polysaccharide, and this is mixed with the denatured bone meal and, if necessary, the bone-forming substances, this dry mixture being mixed with a corresponding amount of the physiological saline solution before use and boiled until sterilization, for example half an hour is enough.

The solution, which has been sterilized by boiling, is then cooled and thermostatically controlled at a temperature above the solidification point until it is used. When applying the solution to an open Knochenwundc care is taken that it is not hot about 50 ⁰ C and having preferably a temperature of about 45 ° C.

According to a variant of the method described above, the sterilized by boiling Solution a substance that promotes tissue diffusion,

gffi ^

special hyaluronids in an amount of 7 IU to 800 IU, preferably 60 [.U. to 90 IU per cm ^{1 of} the solution, and / or 0.05 mg to 500 mg of an antibiotic and / or sulfonamide per cm ^{J of} the solution at a temperature above the solidification temperature of the gel and below the thermal damage point for the substances mentioned lies.

As polysaccharides are expediently Agar products or agar derivatives, in particular agar rose, used. The agarose is expediently as agarose powder in proportions of 0.6% by weight to 30% by weight, preferably 2% by weight to 2.5% by weight, with mixed physiological saline solution - with the denatured bone meal and / r or bone-forming substances are added - and then boiled in a sterile manner.

For the practical use of the agent, it is advantageous if the sterilized solution of physiological saline solution and at least one polysaccharide and / or gelatin and, if necessary, denatured bone meal and / or substances promoting bone wax is filled into disposable syringes. The syringes filled with the liquid solution are stored at a temperature which is above the solidification point of the solution to form the gel, and are ready for direct use. It is also possible to cool the sterilized solution in Jen syringes and thus allow it to solidify. In this case, the syringes have to be heated with the sterilized in their situated solution again so over the Hysleresepunkt of the gel, which is done, for example, that are the syringes and their contents for a period of about 5 minutes in boiling water. The gelling and reliquefaction should, however, not be repeated if possible, as this results in an aging of the agent which worsens its properties.

If tissue diffusion-promoting to the invention means substances and / or antibiotics corresponds ao to hold, it is necessary, however, the sterilized and already cooled; Involvement just this to avoid thermal damage still above the solidification temperature contained solution. At the same time denatured bone meal and / or bone growth-promoting substances can be added if these were not already added when the at least one polysaccharide and / or gelatin was cooked with the physiological saline solution.

This can best be achieved by packing batches of the tissue diffusion-promoting agent and / or the antibiotic and / or the bone growth-promoting substances and / or the denatured bone meal, which correspond to the amount of the sterilized solution taken up by a syringe, in a sterile manner in a dry ampoule. The volume of the dry ampoule must be such that it can hold the sterilized solution in a syringe. The sterilized solution before using the ω agent of the invention then injected at a temperature above the solidification temperature to the gel temperature from the respective Einmäl syringe into the opened ampoule, where it is mixed with the therein substances and subse- ι * Bend back into the Einmjl -Syringe with which it is put to its final use, if necessary after a further thermostated intermediate storage, during which, however, the solidification point must not fall below the June gel.

A wide. ·, For sales and practical Use of the aid is a possible variant in it, now the physiological saline solution and the at least one polysaccharide and / or gelatin and optionally denatured bone meal and / or bone growth-promoting substances as well if necessary, also fill the sulfonamide into ampoules before boiling. The ampoules can be up to Using the agent stored, after which its contents are boiled for dissolution and sterilization. The easiest way to do this is to put the ampoules in a boiling water bath the resulting solution, which forms a gel on cooling, is before the solidification temperature is fallen below The gel is drawn into a disposable syringe, in which one of the quantities contained in each ampoule is already placed corresponding batch of the tissue diffusion promoting agent and / or the antibiotic and / or the bone growth-promoting substance and / or the denatured bone meal and optionally the Sulphonamids is bottled.

If the sterilized, yellowing solution in the ampoule is not used immediately, After cooling and solidification, it can be liquefied again by reheating and for a Use to be provided. However, this process is not for the reasons already mentioned repeatable as often as required. However, once the sterilized gel-forming solution with the tissue diffusion-promoting Agent and / or the antibiotic is mixed, a reprocessing after solidification is separated to the gel, as the tissue diffusion-promoting agents and the antibiotics by heating on the Liquefaction temperature of the gel are destroyed and lose their effectiveness.

With the aid of the agent according to the invention, the alveolus resulting from tooth extraction can be removed fill in, whereby after the liquid solution has cooled down to body temperature, a "gel plug" which prevents the penetration of bacteria and closes the wound. The emergence of a This reliably prevents "dry alveoli". Also the likelihood of rebleeding and Swelling is significantly reduced. The bone growth promoting substances and / or the Denatured bone meal leads to rapid callus formation and less shrinkage of the Bone. The tissue diffusion-promoting substances and / or an antibiotic or a sulfonamide accelerate the healing process of the bone and tissue.

If in the alveolus of the extracted tooth, possibly after deepening the same, in endosseous Dental half-implant is to be used first and immediately after the extraction and optionally a hemostasis with the inventive Medium-soaked gauze strip or tampon pressed into the alveolus The gel-soaked gauze strip is necessary in preparation for the actual implantation process or the tampon is removed and the implant is wiped out again after the wound surface has been streaked out again Agents according to the invention used. Due to the homogeneous sealing of the wound surface, the length of time between extraction and implantation can be up to about 14 days.

The following examples are provided for further explanation the invention:

Example I.

2 g of agarose powder are boiled with 100 ml of physiological saline solution for half an hour. 2 cm ³ of the obtained sterilized solution are mixed and about 10 mg Terramycinpuder and thermostated until use maintained at a temperature of 50 ⁰ C after cooling to 50 ⁰ G 150 IU Hyalurohidäse (Schering product »Kinetinitder). The material would be used for the insertion of intra-osseous dental half-implants.

Kl

Example 2

2 cm ^{3 of} the solution prepared according to Example I are additionally mixed with about 20 mg of powdered apatite crystals, so that a solution is formed which is particularly suitable for inserting implants.

Example 3

2 cm ^{3 of} the solution according to Example 1 are mixed with 0.7 g of denatured bone meal. The solution obtained is used in particular to fill cavities that arise in osseous operations;

The sterilized solution is removed with a 2 cm 'glass syringe. The additives are ^{sterilized in 2 cm 3} dry ampoules.

IX 245/224

y.yp ^ r! jTfrjY T · ^ M

Claims (10)

Patent claims: I. Means for covering and / or filling in bone ends, in particular for inserting Endosseous implants, characterized i by a solution of physiological saline solution and at least one gellable polysaccharide and / or gelatin, the solution being liquid Is at a temperature that is above body temperature, but below a temperature at in which the body tissue is permanently damaged or coagulated, and when it cools down to body temperature forms a stable gel. 2. Agent according to claim 1, characterized by the addition of a substance that promotes tissue diffusion, in particular hyaluronidase in an amount of 7 IU to 800 IU, preferably 60 IU to 90 IU per cm ^{3 of} the liquefied agent. 3rd middle! according to claim! or 2, characterized by the addition of 0.05 mg to about 500 mg of an antibiotic and / or sulfonamide per cm ^{3 of} the liquefied agent. 4. Composition according to one of the preceding claims, characterized by an addition of bone growth-promoting Substances. 5. Composition according to claim 4, characterized in that the bone growth-promoting substances Contains apatite crystals in powder form. 6. Composition according to claim 4 or 5, characterized in that the bone wax promoting Substances sodium, lithium, magnesium, borate, fluoride, phosphate, calcium, potassium ions, Contain carbon and / or silicon compounds in body-soluble form. 7. Agent according to one of the preceding claims, J5 characterized by the addition of 2.5% by weight to 60% by weight, preferably 5% by weight to 20% by weight of a denatured bone meal, based on the amount of the liquefied agent. 8. Agent according to one of the preceding claims, -to characterized in that agar products or agar derivatives are used as polysaccharides. 9. Composition according to claim 8, characterized in that agarose is used as the polysaccharide. 10. Agent according to claim 9, characterized by a 0.6% by weight to 30% by weight, preferably 2% by weight to 2.5% by weight solution of agarose in physiological saline solution.